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尿中多环芳烃代谢物对血脂谱的影响:氧化应激是否起关键介导作用?

The Effect of Urinary Polycyclic Aromatic Hydrocarbon Metabolites on Lipid Profiles: Does Oxidative Stress Play a Crucial Mediation Role?

作者信息

Wang Yuting, Xu Jia, Yang Liujie, Zhang Nan, Zhang Liwen, Han Bin

机构信息

Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

出版信息

Toxics. 2024 Oct 15;12(10):748. doi: 10.3390/toxics12100748.

Abstract

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites are associated with oxidative stress; however, epidemiological studies have not reported the impacts of these urinary PAH metabolites on blood lipid levels. This study investigated the relationship between urinary PAH metabolites, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and blood lipid profiles. A total of 109 elderly volunteers were recruited with complete datasets for analysis. Blood and morning urine samples were collected in the winter of 2011. The PAH metabolites, creatinine, and 8-OHdG levels in urine samples were analyzed using Gas Chromatography-Mass Spectrometry, spectrophotometry, and an ELISA kit, respectively. The blood lipid profiles were analyzed using an automatic biochemical analyzer. The relationship between lipid profiles and 8-OHdG was assessed using a two-independent sample nonparametric test, categorized by gender, smoking, and alcohol consumption status. After normalizing the concentration values, a general linear regression model was employed to examine the correlations between PAH metabolites, 8-OHdG, and lipid profiles. A mediation model was developed to investigate the mediating effect of 8-OHdG on the relationship between PAH metabolites and lipid profiles. The median of eight PAH metabolite concentrations in urine samples ranged from 1 to 10 μmol/mol creatinine (Cr). Significant differences in lipid profiles were observed across genders. However, no significant differences were found in smoking or alcohol consumption status for both genders. Linear regression analysis revealed that an increase in the logarithmic concentration of 2-hydroxynaphthalene (2-OHNap), 9-hydroxyfluorene (9-OHFlu), 3-hydroxyfluorene (3-OHFlu), 2-hydroxyfluorene (2-OHFlu), 1-hydroxypyrene (1-OHPyr), and 6-hydroxychrysene (6-OHChr) was associated with an increase in urinary 8-OHdG levels, after adjusting for BMI and age. Specifically, 1-hydroxynaphthalene (1-OHNap) and 1-OHPyr correlated negatively with apolipoprotein A1 (Apo A1). Conversely, 1-OHPyr was positively correlated with low-density lipoprotein cholesterol (LDL-C). In addition, b,c-dihydroxyphenanthrene (2-OHBcPhe) was positively associated with apolipoprotein B (Apo B). Notably, 8-OHdG did not exhibit a significant correlation with lipid profiles. The mediating effect of 8-OHdG on the relationship between hydroxylated PAHs and lipid profiles was not statistically significant. However, the indirect effects of hydroxylated PAHs on blood lipids were statistically substantial, specifically for 1-OHNap to Apo A1 (-0.025, 95% CI: -0.041, -0.009), 1-OHPyr to LDL-C (0.107, 95% CI: 0.011, 0.203), and 2-OHBcPhe to Apo B (0.070, 95% CI: 0.005, 0.135). This study suggests that an increase in urinary PAH metabolites may elevate the levels of urinary 8-OHdG and influence blood lipid profiles. However, no direct relationship was found between 8-OHdG and lipid profiles. The mediation analysis indicated that the effects of PAH metabolites on lipid changes may operate through pathways other than oxidative stress.

摘要

尿多环芳烃(PAH)代谢物与氧化应激相关;然而,流行病学研究尚未报道这些尿PAH代谢物对血脂水平的影响。本研究调查了尿PAH代谢物、尿8-羟基-2'-脱氧鸟苷(8-OHdG)与血脂谱之间的关系。共招募了109名老年志愿者,其数据集完整可供分析。于2011年冬季采集血液和晨尿样本。分别采用气相色谱-质谱联用仪、分光光度法和酶联免疫吸附测定试剂盒分析尿样中的PAH代谢物、肌酐和8-OHdG水平。使用自动生化分析仪分析血脂谱。采用两独立样本非参数检验评估血脂谱与8-OHdG之间的关系,并按性别、吸烟和饮酒状况进行分类。在对浓度值进行标准化后,采用一般线性回归模型检验PAH代谢物、8-OHdG与血脂谱之间的相关性。建立中介模型以研究8-OHdG在PAH代谢物与血脂谱关系中的中介作用。尿样中8种PAH代谢物浓度的中位数范围为1至10 μmol/mol肌酐(Cr)。不同性别之间血脂谱存在显著差异。然而,在吸烟或饮酒状况方面,两性均未发现显著差异。线性回归分析显示,在调整体重指数(BMI)和年龄后,2-羟基萘(2-OHNap)、9-羟基芴(9-OHFlu)、3-羟基芴(3-OHFlu)、2-羟基芴(2-OHFlu)、1-羟基芘(1-OHPyr)和6-羟基 Chrysene(6-OHChr)的对数浓度增加与尿8-OHdG水平升高相关。具体而言,1-羟基萘(1-OHNap)和1-OHPyr与载脂蛋白A1(Apo A1)呈负相关。相反,1-OHPyr与低密度脂蛋白胆固醇(LDL-C)呈正相关。此外,b,c-二羟基菲(2-OHBcPhe)与载脂蛋白B(Apo B)呈正相关。值得注意的是,8-OHdG与血脂谱未显示出显著相关性。8-OHdG在羟基化多环芳烃与血脂谱关系中的中介作用无统计学意义。然而,羟基化多环芳烃对血脂的间接作用具有统计学显著性,特别是1-OHNap对Apo A1(-0.025,95%置信区间:-0.041,-0.009)、1-OHPyr对LDL-C(0.107,95%置信区间:0.011,0.203)以及2-OHBcPhe对Apo B(0.070,95%置信区间:0.005,0.135)。本研究表明,尿PAH代谢物增加可能会提高尿8-OHdG水平并影响血脂谱。然而,未发现8-OHdG与血脂谱之间存在直接关系。中介分析表明,PAH代谢物对血脂变化的影响可能通过氧化应激以外的途径起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5592/11511148/f8d1d00983ee/toxics-12-00748-g001.jpg

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